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Trial record 10 of 20 for:    PKU | Boston, Massachusetts, U.S.

Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU (Prism302)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01889862
Recruitment Status : Completed
First Posted : July 1, 2013
Results First Posted : July 12, 2019
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Phenylketonuria (PKU)
Interventions Drug: BMN165 20mg/day
Drug: BMN165 40mg/day
Drug: Placebo
Enrollment 215
Recruitment Details Only subjects who completed a previous pegvaliase study (i.e. PAL-003, 165-205, or 165-301) were eligible for participation in 165-302.
Pre-assignment Details Pt 1 (3-13wk) was an open-label period to establish eligibility for participation in Pt 2. Eligible subjects (achieve and maintain randomized dose of 20 or 40mg/day and ≥20% reduction in blood Phe) enrolled into Part 2 (8wk). Subjects completing Pt 2 were eligible for Pt 3 (6wk). Part 4 is ongoing. Pt 2 results are currently shown (n=95).
Arm/Group Title BMN165 20mg/Day (Part 2) 20 mg/Day Placebo (Part 2) BMN165 40mg/Day (Part 2) 40 mg/Day Placebo (Part 2)
Hide Arm/Group Description

BMN165 20mg/day self-administered daily

BMN165 20mg/day: BMN165 20mg/day self-administered daily

20 mg/day Placebo self-administered daily

Placebo: Two different doses of BMN165 compared to each other and compared to placebo

BMN165 40mg/day self-administered daily

BMN165 40mg/day: BMN165 40mg/day self-administered daily

40 mg/day Placebo self-administered daily

Placebo: Two different doses of BMN165 compared to each other and compared to placebo

Period Title: Overall Study
Started [1] 34 15 32 14
Completed [1] 34 15 31 14
Not Completed 0 0 1 0
[1]
Though 215 subjects enrolled, only Part 2's 95 subjects have results reported. Thus the discrepancy.
Arm/Group Title BMN165 20mg/Day 20 mg/Day Placebo BMN165 40mg/Day 40 mg/Day Placebo Total
Hide Arm/Group Description BMN165 20mg/day self-administered daily 20 mg/day Placebo self-administered daily BMN165 40mg/day self-administered daily 40 mg/day Placebo self-administered daily Total of all reporting groups
Overall Number of Baseline Participants 34 15 32 14 95
Hide Baseline Analysis Population Description
Only Part 2 patient results were analyzed and are presented as they completed the primary endpoint.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 15 participants 32 participants 14 participants 95 participants
32.3  (9.29) 32.1  (10.56) 30.1  (7.95) 30.8  (10.30) 31.3  (9.13)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 15 participants 32 participants 14 participants 95 participants
16 - <18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
18 - <66 years
34
 100.0%
15
 100.0%
32
 100.0%
14
 100.0%
95
 100.0%
>= 66 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 15 participants 32 participants 14 participants 95 participants
Female
15
  44.1%
6
  40.0%
17
  53.1%
6
  42.9%
44
  46.3%
Male
19
  55.9%
9
  60.0%
15
  46.9%
8
  57.1%
51
  53.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 15 participants 32 participants 14 participants 95 participants
Hispanic or Latino
1
   2.9%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Not Hispanic or Latino
33
  97.1%
15
 100.0%
32
 100.0%
14
 100.0%
94
  98.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 15 participants 32 participants 14 participants 95 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
1
   1.1%
White
34
 100.0%
14
  93.3%
32
 100.0%
14
 100.0%
94
  98.9%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Plasma Phenylalanine (Phe) Levels
Hide Description Subjects will be assessed every 4 weeks for plasma Phe levels.
Time Frame Part 2 baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat (mITT) population (all subjects randomized in Part 2 with a mean blood Phe reduction of ≥20% (using the last two consecutive blood Phe assessments of Part 1) from baseline levels of Study 165-301 or the Phase 2 study in which they initiated BMN 165)
Arm/Group Title BMN165 20mg/Day 20 mg/Day Placebo BMN165 40mg/Day 40 mg/Day Placebo
Hide Arm/Group Description:

BMN165 20mg/day self-administered daily

BMN165 20mg/day: BMN165 20mg/day self-administered daily

20 mg/day Placebo self-administered daily

Placebo: Two different doses of BMN165 compared to each other and compared to placebo

BMN165 40mg/day self-administered daily

BMN165 40mg/day: BMN165 40mg/day self-administered daily

40 mg/day Placebo self-administered daily

Placebo: Two different doses of BMN165 compared to each other and compared to placebo

Overall Number of Participants Analyzed 29 14 29 14
Mean (Standard Deviation)
Unit of Measure: umol/L
Part 2 Baseline Number Analyzed 29 participants 14 participants 29 participants 14 participants
596.8  (582.75) 563.9  (504.62) 410.9  (439.95) 508.2  (363.68)
Part 2 Week 8 Number Analyzed 26 participants 13 participants 23 participants 10 participants
553.0  (582.39) 1509.0  (372.64) 566.3  (567.47) 1164.4  (343.32)
2.Secondary Outcome
Title Cognitive and Mood Symptoms BMN 165
Hide Description ADHD-RS IV and the POMS (Profile of Mood States) will be used to evaluate cognitive and mood symptoms.
Time Frame Throughout the study
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Plasma Phenylalanine (Phe) Levels
Hide Description [Not Specified]
Time Frame Throughout the study
Outcome Measure Data Not Reported
4.Other Pre-specified Outcome
Title Protein Intake as Reported by Subjects in Diet Diary
Hide Description Diet diary collected monthly to assess protein intake from medical food and from natural protein.
Time Frame Every 4 weeks, throughout study
Outcome Measure Data Not Reported
Time Frame Week 0- Week 8
Adverse Event Reporting Description Part 2 data shown only. Study remains ongoing.
 
Arm/Group Title BMN165 20mg/Day 20 mg/Day Placebo BMN165 40mg/Day 40 mg/Day Placebo
Hide Arm/Group Description BMN165 20mg/day self-administered daily 20 mg/day Placebo self-administered daily BMN165 40mg/day self-administered daily 40 mg/day Placebo self-administered daily
All-Cause Mortality
BMN165 20mg/Day 20 mg/Day Placebo BMN165 40mg/Day 40 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/34 (0.00%)      0/15 (0.00%)      0/32 (0.00%)      0/14 (0.00%)    
Hide Serious Adverse Events
BMN165 20mg/Day 20 mg/Day Placebo BMN165 40mg/Day 40 mg/Day Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/34 (0.00%)      1/15 (6.67%)      2/32 (6.25%)      0/14 (0.00%)    
Investigations         
Blood creatine phosphokinase increased  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Psychiatric disorders         
Agitation  1  0/34 (0.00%)  0 0/15 (0.00%)  0 1/32 (3.13%)  1 0/14 (0.00%)  0
Depression  1  0/34 (0.00%)  0 0/15 (0.00%)  0 1/32 (3.13%)  1 0/14 (0.00%)  0
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BMN165 20mg/Day 20 mg/Day Placebo BMN165 40mg/Day 40 mg/Day Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/34 (79.41%)      13/15 (86.67%)      28/32 (87.50%)      13/14 (92.86%)    
Blood and lymphatic system disorders         
Lymphadenopathy  1  1/34 (2.94%)  1 0/15 (0.00%)  0 0/32 (0.00%)  0 2/14 (14.29%)  2
Ear and labyrinth disorders         
Ear pain  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Tinnitus  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Vertigo  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Eye disorders         
Blepharospasm  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Gastrointestinal disorders         
Abdominal discomfort  1  1/34 (2.94%)  1 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Abdominal pain  1  2/34 (5.88%)  5 0/15 (0.00%)  0 0/32 (0.00%)  0 0/14 (0.00%)  0
Abdominal pain upper  1  1/34 (2.94%)  1 0/15 (0.00%)  0 1/32 (3.13%)  1 1/14 (7.14%)  1
Constipation  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 1/14 (7.14%)  1
Diarrhoea  1  2/34 (5.88%)  2 0/15 (0.00%)  0 2/32 (6.25%)  2 0/14 (0.00%)  0
Gastrooesophageal reflux disease  1  0/34 (0.00%)  0 1/15 (6.67%)  1 2/32 (6.25%)  2 1/14 (7.14%)  1
Nausea  1  4/34 (11.76%)  4 1/15 (6.67%)  1 1/32 (3.13%)  1 1/14 (7.14%)  2
Vomiting  1  1/34 (2.94%)  1 0/15 (0.00%)  0 1/32 (3.13%)  1 1/14 (7.14%)  1
General disorders         
Chest discomfort  1  2/34 (5.88%)  4 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Fatigue  1  4/34 (11.76%)  6 3/15 (20.00%)  3 3/32 (9.38%)  3 0/14 (0.00%)  0
Feeling abnormal  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Inflammation  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Injection site bruising  1  2/34 (5.88%)  4 2/15 (13.33%)  4 1/32 (3.13%)  1 1/14 (7.14%)  1
Injection site erythema  1  2/34 (5.88%)  10 0/15 (0.00%)  0 2/32 (6.25%)  8 0/14 (0.00%)  0
Injection site haemorrhage  1  1/34 (2.94%)  1 0/15 (0.00%)  0 2/32 (6.25%)  16 0/14 (0.00%)  0
Injection site pain  1  1/34 (2.94%)  4 1/15 (6.67%)  1 1/32 (3.13%)  24 0/14 (0.00%)  0
Injection site reaction  1  4/34 (11.76%)  20 1/15 (6.67%)  1 1/32 (3.13%)  1 1/14 (7.14%)  1
Injection site swelling  1  2/34 (5.88%)  25 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  2
Immune system disorders         
Seasonal allergy  1  0/34 (0.00%)  0 0/15 (0.00%)  0 2/32 (6.25%)  2 0/14 (0.00%)  0
Infections and infestations         
Bronchitis  1  1/34 (2.94%)  1 1/15 (6.67%)  1 1/32 (3.13%)  1 1/14 (7.14%)  1
Conjunctivitis  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Ear infection  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Fungal skin infection  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Laryngitis  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Nasopharyngitis  1  4/34 (11.76%)  4 0/15 (0.00%)  0 1/32 (3.13%)  1 1/14 (7.14%)  1
Pharyngitis streptococcal  1  0/34 (0.00%)  0 0/15 (0.00%)  0 1/32 (3.13%)  1 1/14 (7.14%)  1
Upper respiratory tract infection  1  1/34 (2.94%)  1 3/15 (20.00%)  3 0/32 (0.00%)  0 2/14 (14.29%)  2
Urinary tract infection  1  2/34 (5.88%)  2 0/15 (0.00%)  0 0/32 (0.00%)  0 0/14 (0.00%)  0
Injury, poisoning and procedural complications         
Contusion  1  1/34 (2.94%)  1 2/15 (13.33%)  6 1/32 (3.13%)  1 0/14 (0.00%)  0
Muscle strain  1  1/34 (2.94%)  1 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Post-traumatic pain  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Road traffic accident  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Skin abrasion  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Investigations         
Blood bilirubin increased  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Blood creatine phosphokinase increased  1  0/34 (0.00%)  0 1/15 (6.67%)  1 1/32 (3.13%)  1 1/14 (7.14%)  1
Complement factor C3 decreased  1  2/34 (5.88%)  2 0/15 (0.00%)  0 0/32 (0.00%)  0 0/14 (0.00%)  0
Weight decreased  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Weight increased  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Metabolism and nutrition disorders         
Hypoglycaemia  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Musculoskeletal and connective tissue disorders         
Arthralgia  1  7/34 (20.59%)  49 1/15 (6.67%)  1 2/32 (6.25%)  13 2/14 (14.29%)  2
Back pain  1  0/34 (0.00%)  0 1/15 (6.67%)  1 1/32 (3.13%)  1 1/14 (7.14%)  1
Myalgia  1  0/34 (0.00%)  0 1/15 (6.67%)  1 2/32 (6.25%)  2 0/14 (0.00%)  0
Pain in extremity  1  1/34 (2.94%)  1 0/15 (0.00%)  0 1/32 (3.13%)  1 1/14 (7.14%)  1
Nervous system disorders         
Disturbance in attention  1  4/34 (11.76%)  4 2/15 (13.33%)  2 1/32 (3.13%)  1 0/14 (0.00%)  0
Dizziness  1  1/34 (2.94%)  1 1/15 (6.67%)  2 2/32 (6.25%)  2 0/14 (0.00%)  0
Dyspraxia  1  1/34 (2.94%)  1 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Headache  1  6/34 (17.65%)  15 3/15 (20.00%)  4 2/32 (6.25%)  2 4/14 (28.57%)  9
Hyperreflexia  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Lethargy  1  0/34 (0.00%)  0 2/15 (13.33%)  2 0/32 (0.00%)  0 0/14 (0.00%)  0
Memory impairment  1  3/34 (8.82%)  3 0/15 (0.00%)  0 0/32 (0.00%)  0 0/14 (0.00%)  0
Migraine  1  0/34 (0.00%)  0 1/15 (6.67%)  4 2/32 (6.25%)  2 0/14 (0.00%)  0
Paraesthesia  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Sciatica  1  1/34 (2.94%)  1 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Somnolence  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Tremor  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 1/14 (7.14%)  1
Psychiatric disorders         
Agitation  1  0/34 (0.00%)  0 0/15 (0.00%)  0 3/32 (9.38%)  5 0/14 (0.00%)  0
Anxiety  1  4/34 (11.76%)  4 0/15 (0.00%)  0 3/32 (9.38%)  5 2/14 (14.29%)  2
Depression  1  1/34 (2.94%)  1 2/15 (13.33%)  2 1/32 (3.13%)  1 0/14 (0.00%)  0
Depressive symptom  1  2/34 (5.88%)  2 0/15 (0.00%)  0 0/32 (0.00%)  0 0/14 (0.00%)  0
Distractibility  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Emotional disorder  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Insomnia  1  1/34 (2.94%)  1 0/15 (0.00%)  0 3/32 (9.38%)  3 0/14 (0.00%)  0
Irritability  1  0/34 (0.00%)  0 2/15 (13.33%)  2 2/32 (6.25%)  3 1/14 (7.14%)  1
Mood altered  1  0/34 (0.00%)  0 0/15 (0.00%)  0 1/32 (3.13%)  1 2/14 (14.29%)  2
Renal and urinary disorders         
Ketonuria  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Proteinuria  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Urine odour abnormal  1  0/34 (0.00%)  0 1/15 (6.67%)  1 0/32 (0.00%)  0 0/14 (0.00%)  0
Reproductive system and breast disorders         
Dysmenorrhoea  1  3/34 (8.82%)  8 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 2/14 (14.29%)  2
Nasal congestion  1  1/34 (2.94%)  1 3/15 (20.00%)  4 0/32 (0.00%)  0 0/14 (0.00%)  0
Oropharyngeal pain  1  1/34 (2.94%)  1 0/15 (0.00%)  0 1/32 (3.13%)  2 1/14 (7.14%)  1
Rhinorrhoea  1  0/34 (0.00%)  0 0/15 (0.00%)  0 0/32 (0.00%)  0 1/14 (7.14%)  1
Sinus congestion  1  2/34 (5.88%)  2 0/15 (0.00%)  0 1/32 (3.13%)  1 0/14 (0.00%)  0
Skin and subcutaneous tissue disorders         
Alopecia  1  2/34 (5.88%)  2 2/15 (13.33%)  2 0/32 (0.00%)  0 1/14 (7.14%)  1
Pruritus  1  1/34 (2.94%)  1 0/15 (0.00%)  0 4/32 (12.50%)  6 1/14 (7.14%)  1
Rash  1  2/34 (5.88%)  4 1/15 (6.67%)  1 3/32 (9.38%)  4 0/14 (0.00%)  0
Urticaria  1  2/34 (5.88%)  5 0/15 (0.00%)  0 1/32 (3.13%)  1 0/14 (0.00%)  0
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Senior Medical Director
Organization: BioMarin Pharmaceutical Inc
Phone: 415-475-5854
EMail: ari.gershman@bmrn.com
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01889862    
Other Study ID Numbers: 165-302
First Submitted: June 18, 2013
First Posted: July 1, 2013
Results First Submitted: June 22, 2018
Results First Posted: July 12, 2019
Last Update Posted: August 2, 2019